Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia

Abstract

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph-neg adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15-60 years (y) with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation, were assigned to receive delayed consolidation and maintenance therapy up to 2y in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95%CI) cumulative incidence of relapse (CIR), overall survival (OS) and event-free survival (EFS) probabilities for the whole series were 43%±7%, 49%±7% and 40±6%, respectively, with CIR and OS rates of 45±8% and 59±9% for patients assigned to chemotherapy and of 40±12% and 38±11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph-neg adult ALL patients up to 60y with adequate MRD response after induction and consolidation. Better post-remission alternative therapies are especially needed for patients with poor MRD clearance. ClinicalTrials.gov (NCT01540812)

Outcomes and prognostic factors of adults with refractory or relapsed T‐cell acute lymphoblastic leukemia included in measurable residual disease‐oriented trials

“…Patients with good MRD clearance after early consolidation continued with delayed consolidation and maintenance therapy, whereas those with poor MRD clearance were allocated to allogeneic hematopoietic stem cell transplantation (HSCT). The characteristics and results of both protocols have already been published 21,22 . Patients with isolated CNS relapse were treated with triple intrathecal therapy (TIT) every 3–4 days until blast clearance, plus two additional doses, with a minimum dose number of five.…”

“…The characteristics and results of both protocols have already been published. 21,22 Patients with isolated CNS relapse were treated with triple intrathecal therapy (TIT) every 3-4 days until blast clearance, plus two additional doses, with a minimum dose number of five. Simultaneously patients received systemic therapy, mainly with drugs passing the blood-brain barrier.…”

MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL

“…However, with few exceptions, MRD was not assessable in about one fourth of CR patients, due to either an insufficient diagnostic and/or follow-up sampling or a failure to generate a molecular probe, while, in this regard, the search for a case-specific LAIP was less troublesome, with success rates >95% when it was applied systematically [ 35 , 40 , 49 ]. Performing an adequate ALL cell sampling may become a highly critical issues, because, in some studies, only 50% or less of the patients underwent MRD analysis [ 26 , 37 ], or this same figure was slightly above 50% in others [ 41 , 44 ].…”

Flow cytometric minimal residual disease assessment in B‐cell precursor acute lymphoblastic leukaemia patients treated with CD19‐targeted therapies — a EuroFlow study

“…Minimal residual disease (MRD) is used as an important prognostic biomarker in B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL) treatment protocols 1 . In Europe, MRD levels are generally assessed by real‐time quantitative polymerase chain reaction (RQ‐PCR) analysis of immunoglobulin and/or T‐cell receptor gene rearrangements, 2 but in more recent protocols MRD is also being evaluated by flow cytometry 3,4 . A standardized protocol for flow cytometric MRD assessment in BCP‐ALL was developed by the EuroFlow consortium 5 .…”